FasL is a type II membrane protein belonging to the TNF family, which induces apoptosis in Fas-bearing cells. FasL can be cleaved off from the membrane by a metalloprotease(s). and the soluble FasL displays a much lower cytotoxic activity than its membrane-bound form. FasL is one of the effector molecules of cytotoxic T cells and NK cells. FasL is also expressed in stroma cells of the eye. and contributes to the eye's privileged immune status. The murine gld (generalized lymphoproliferative disease) mutation is a loss-of-function mutation of FasL. The mice develop lympha-(tenopathy and splenomegaly, produce a large amount of immunoglobulin, and develop autoimmune diseases. Administration of FasL into these mice causes hepatitis, and quickly kills them. CTL-induced hepatitis or graft-versus-ho st disease can be inhibited by soluble Fas or neutralizing anti-FasL antibody, suggesting that various forms of CTL-induced tissue destruction are probably caused by о verexpression of FasL.

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